Gastric mucosa behaves analogously to other secreting tissues in that cyclic nucleotides undergo transient changes during sustained stimulation by secretagogues., i.e., histamine and acetylcholine. These findings from this laboratory confirm the expectations expressed in the previous proposal and lead to further questions about the details of the processes associated with biochemical signal transmission. Preliminary binding studies indicate a difference between binding of histamine and its antagonist. In this study I propose to investigate time dependency and dose-response of biochemical variables to secretagogues and their antagonists in tissues and their cellular components. As a primary secretagogue histamine will be used. Since pentagastrin and acetylcholine stimulation lead to increased histamine secretion, their role in acid and/or alkaline secretion or oxygen consumption will also be studied. In addition the effects of H2-antagonists and anticholinergic agents will be investigated. In particular the relationship between histamine secretion and acid secretion will be explored. The following biochemical variables will be observed: adenylate and guanylate cyclase activities, cyclic AMP and GMP, phosphodiesterase and protein kinase activities. Special attention will be given to the time course of changes in these variables to elucidate which of them, if any, might be transient as opposed to sustained. Their dose response characteristics will be related to receptor binding parameters of secretagogues and their antagonists.